Many effective growth factors and other bioactive agents have been developed to help in tissue repair and in treating diseases by applying them to a localized area, such as a surgical site. Conventional methods of delivering growth factors and/or other bioactive agents utilize many types of drug delivery technologies.
Current drug delivery technologies utilize different carriers such as polymeric matrices, microencapsulation, or collagen sponges. In general, polymeric matrix or microencapsulation techniques require the incorporation of the bioactive agent into a carrier at a production facility. While release characteristics can be usually controlled, generally the materials used for carriers fail to promote tissue repair and growth.
Collagen sponges are frequently used as scaffolds for tissue growth, but normally the bioactive agent is added to the sponge at the point of use. In nature, a bioactive agent such as bone morphogenic proteins are found bound to collagen. Although, collagen is a very good carrier for bone morphogenic proteins, when bone morphogenic proteins are added to collagen sponges, the original bonding found in nature is not recreated and, as a result the bone morphogenic proteins are only physically incorporated in the collagen sponges and become released too quickly, thereby failing to retain their full efficacy.
Sometimes when the surgeon manipulates the matrix to place it in the bone defect, excessive amounts of growth factor (e.g., bone morphogenic protein) may leak or migrate from the matrix, which may reduce a stable microenvironment for new bone and/or cartilage growth. This migration of the bioactive agent may also cause the collagen sponge to fail to retain its full efficacy over time to maximally promote bone and/or cartilage growth at a target site, side effects can be exaggerated and dosages required for treatment become uneconomically large.
Thus, there is a need to develop new osteogenic compositions and methods that improve bone and/or cartilage repair by retaining bone morphogenic proteins and other growth factors much longer than prior art collagen sponges. It is, therefore, desirable to provide methods of preparing bone material having increased surface area, increased biological activities including but not limited to osteoinductive activity. Further, it is also desirable to provide bone implants prepared from bone material having enhanced osteoinductivity and enhanced ability to grow and integrate into a host bone.